Crescentic Glomerulonephritis Requiring Hemodialysis and Elevated MPO-ANCA Level and Vasculitis Allergica Cutis in a 21-Year-Old Girl

Ismail H. Kara, MD; M. Emin Yilmaz, MD; Yasin Sari, MD; Ali Gür, MD; Hüseyin Büyükbayram, MD

Disclosures

May 01, 2002

Discussion

mPA, previously called hypersensitivity angiitis, is a systemic necrotizing vasculitis that involves many organ systems, including the skin, joints, kidneys, and lungs. mPA most commonly affects adults in the fourth and fifth decades of life, with only a few cases reported in children.[8] It was first recognized and distinguished from polyarteritis nodosa in the 1950s by its involvement of vessels smaller than arteries.[2,9] It was distinguished from WG in the 1980s based on the differences in lung abnormalities. CSS is usually associated with asthma and eosinophil-rich granulomatous inflammation of the respiratory tract. However, the accurate diagnosis of CSS remains problematic, in that approximately one half to two thirds of reported patients with CSS are ANCA positive.[3,4] An analysis of the association between CSS and ANCA is difficult, because various studies have used different diagnostic criteria for CSS, as well as varied methods in the performance and interpretation of ANCA assays. Other forms of vasculitis, including Takayasu arteritis, Henoch-Schönlein purpura, and cryoglobulinemia, are generally not associated with the presence of ANCA.[5,10,11,12]

The early symptoms of mPA are nonspecific, such as fever, anorexia, fatigue, arthralgia, myalgia, and weight loss. However, a characteristic feature is RPGN, often seen in the early stages of the condition. Skin lesions include purpura and splinter hemorrhages, which occur in 50% of patients. Serum complement components are in the normal range and cryoimmunoglobulins and rheumatoid factors are usually not found in the circulation. However, Ig levels may be increased.[7,9,13,14]

In this case, weight loss, anemia, fever, rash (including an erythematous maculopapular eruption, vasculitic ulcers, and painful subcutaneous nodules), severe myalgia, and a migratory nonerosive polyarthritis were present (Figure 1). Other laboratory findings were similar to those in the literature, such as elevated IgE, ESR, and CRP levels, but normal complement and cryoglobulin levels. Although we did not see some conditions such as nasal polyposis, obstruction, and recurrent sinusitis, serous otitis history was present. In our case, mild hematuria (8-10 RBC/hpf) but heavy albuminuria (5.5 g/day) were present. Renal involvement was to become more predominate. In spite of combined treatment of disease, BUN and creatinine levels steadily increased, requiring hemodialysis. However, several series have reported a considerable degree of renal involvement.[15,16,17]

mPA can affect the gastrointestinal tract in 30% of cases and result in abdominal pain, diarrhea, and bleeding. Peripheral neuropathy occurs in about a third of patients. Myalgias and arthralgias are present in up to 70% of patients, whereas frank arthritis is less common.[14,18,19] Kandeel and colleagues[8] also reported that a 17-year-old male with mPA had c-ANCA titers that were positive at 1:100, and tests for p-ANCA and anti-GBM antibodies were negative. The chest x-ray at admission showed bibasilar infiltrates and no cardiomegaly. A biopsy specimen of the skin rash showed neutrophilic vasculitis involving capillaries, venules, and arterioles. A renal biopsy specimen obtained months after discharge because of persistent hematuria and proteinuria revealed pauci-immune crescentic glomerulonephritis. Kandeel and colleagues reported that respiratory distress of this patient rapidly resolved, the patient was discharged 6 days later while taking daily steroids and cyclophosphamide, and he was completely asymptomatic after 4 weeks.

However, the case of the 21-year-old female described here failed to respond to pulse corticosteroid combined with cytotoxic agent treatment and plasmapheresis. While the patient was undergoing hemodialysis, disease progressed and clinical syndromes involving other organ systems began. Gastrointestinal, peripheral nervous, cardiovascular, and respiratory systems became involved, as evidenced by a lower blood pressure (80/50 mm Hg), painful skin lesions, respiratory distress, abdominal pain, and ascites. Radiologic (chest x-ray, thoracic MRI, and echocardiography) studies revealed only cardiomegaly and persistent minimal bilateral pleural and pericardial effusions.

The typical histopathologic feature of the predominantly cutaneous vasculitides is the presence of vasculitis of small vessels. Postcapillary venules are the most commonly involved vessels; capillaries and arterioles may be involved less frequently. This vasculitis is characterized by a "leukocytoclasis," a term that refers to the nuclear debris remaining from the neutrophils that have infiltrated in and around the vessels during the acute stages.[20,21] ANCA associated glomerulonephritis complicated by VAC, in particular, has been reported previously by Nakabayashi and colleagues.[22] They reported a case of a 69-year-old male with VAC accompanied by a nephrotic syndrome associated with serum MPO-ANCA. Renal biopsy specimens showed mild proliferative glomerulonephritis with crescentic and necrotising lesion in the glomeruli, while lesional skin biopsy specimens showed leukocytoclastic vasculitis in the deep dermis. The case described here also developed similar skin lesions, and was accompanied by a nephrotic syndrome associated with serum MPO-ANCA positivity. Furthermore, renal biopsy specimens showed diffuse proliferative glomerulonephritis with crescentic and necrotising lesions in contrast to Nakabayashi's case report.[22] Photomicrograph of skin biopsy, in the case described here, showed severe necrotizing vasculitis with adjacent leukocyte infiltration and leukocytoclasia, especially round vessels by hematoxylin-eosin stain (Figure 2).

HCV is also the cause of, or is associated with, various dermatologic disorders. The main dermatologic disorders in HCV infection include: (1) vasculitis (mainly cryoglobulin-associated vasculitis); (2) sporadic porphyria cutanea tarda; (3) cutaneous and/or mucosal lichen planus; and (4) salivary gland lesions, characterized by lymphocytic capillaritis, sometimes associated with lymphocytic sialadenitis resembling that of Sjoegren's syndrome. In other dermatologic disorders, HCV serology will be necessary only in case of risk factors for HCV infection, or presence of abnormal liver function tests.[23] In this case, anti-HCV was positive, but HCV RNA PCR was negative, and liver enzyme levels were normal. In addition, the skin biopsy was not related to cryoglobulin-associated vasculitis; therefore, the authors did not consider that skin lesions resulted from activation of HCV.

Attempts to specifically classify patients based on existing schemes may result in delayed diagnosis and therapy, with subsequent poorer outcomes. Also, given the increased mortality of patients with respiratory tract involvement, Cohen and Clark[24] speculated that in cases involving the respiratory tract, therapeutic and monitoring regimens may be ineffective. In general, pauci-immune renal vasculitis is a heterogeneous disorder with an unfavorable prognosis, and relatively rare in children and young adults. To alert people, the authors reported herein a 21-year-old girl with mPA with renal and skin involvement who did not respond well to treatment, required hemodialysis, and had a relatively short-term survival (31 months).

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